Investigational Compound Designed to Disrupt Autoimmune Cascade
BOSTON, November 9 /CNW/ - Biogen Idec today presented results from its
Phase IIa trial of baminercept (LT(beta)R-Ig or BG9924), the first
dual-mechanism, lymphotoxin-(beta) (LT-(beta)) and LIGHT pathway inhibitor in
development for the treatment of autoimmune diseases, including rheumatoid
arthritis (RA). The data suggest clinically meaningful improvements in
American College of Rheumatology (ACR) scores and individual core set
measurements in patients with RA who received baminercept compared with
placebo. Results from the Phase IIa trial were presented at ACR's 73rd Annual
Meeting in Boston.
ACR score improvements persisted for up to eight weeks following the
final study dose and were seen in patients given 1.0 mg/kg or 3.0 mg/kg once a
week subcutaneously for four weeks, the two highest dose groups in the study.
The most common adverse event was headache and no serious adverse events
attributed to the compound were reported during the study period. Safety
results support the continued development of baminercept.
"Pre-clinical studies suggest that baminercept blocks an underlying
disease mechanism associated with inflammation," said Evan Beckman, Senior
Vice President of Immunology Research and Development at Biogen Idec.
"Autoimmune disorders that may be influenced by this mechanism include
multiple sclerosis, lupus and Crohn's disease.We are encouraged that the
results of this trial suggest potential benefits of targeting the LT-b pathway
in developing a new RA treatment option."
Based on the results of this Phase IIa study, Biogen Idec has initiated
two Phase IIb trials to study baminercept in combination with methotrexate in
patients with moderate to severe RA who had an inadequate response to
treatment with a DMARD therapy (disease-modifying antirheumatic drug) or a TNF
inhibitor (biologic therapies that target the TNF pathway).
Rheumatoid Arthritis and the LT-(beta) Pathway
In patients with RA, certain immune cells malfunction and attack the
joints, causing painful and chronic inflammation as well as destruction of
cartilage, tendons and bones. As in other autoimmune diseases, the immune
system mistakes healthy cells for foreign invaders. Though the exact cause of
RA is unknown, new research is uncovering the immunologic and genetic factors
that play important roles in triggering and perpetuating inflammation of the
joints.
As shown in preclinical studies, baminercept is thought to inhibit the
function of LT(alpha)1(beta)2 and LIGHT, two critical components of the
LT-(beta) pathway implicated in the progression of RA and other autoimmune
diseases. These diseases are in part characterized by the inappropriate
emergence of organized immune cell collections, or lymphoid structures, in a
variety of tissues. Baminercept is thought to act by inhibiting the formation
and maintenance of out-of-place, or ectopic, lymphoid structures implicated in
the autoimmune disease cascade. In RA, aberrant immune effector cells may rely
on these ectopic lymphoid structures present in inflamed joints to trigger and
propagate the chronic inflammatory process. By blocking inappropriate signals
from cell-surface LT(alpha)1(beta)2 and LIGHT ligands, baminercept may help
restore a normal immune environment.
The LT-(beta) pathway was discovered at Biogen Idec, and baminercept is a
wholly-owned Biogen Idec molecule that was discovered in collaboration with
academic scientists. Baminercept is one of several programs in the company's
research and development efforts in rheumatology.
Phase IIa Data Results
The Phase IIa blinded, multicenter, placebo-controlled trial was designed
to assess the safety, pharmacokinetics, pharmacodynamics and efficacy of
baminercept with methotrexate, a standard RA therapy, at different dose
ranges. Patients (n=47) were randomized in a dose-escalating fashion to
receive placebo or one of six doses of baminercept, ranging from 0.01 mg/kg to
3.0 mg/kg once weekly for four weeks, followed by eight weeks of observation.
Patients had to have received methotrexate for at least three months prior to
enrollment and continued to receive a stable dose of methotrexate throughout
the study period.
Study results suggested improvement in the majority of ACR core set
measurements (a series of standard measurement criteria for RA symptom and
disease improvement) in patients given baminercept compared with placebo. At
day 35, patients given baminercept showed an average 60 percent improvement
from baseline in swollen joint count and 47 percent improvement in tender
joint count, compared with 4.6 percent and 6.7 percent with placebo,
respectively. Improvements in these ACR measures persisted for eight weeks
after the final baminercept dose.
Similar levels of improvements were observed at day 35 in several other
standard markers of inflammation and disease progression. ACR scores and other
measures improved in a dose dependent manner, with the greatest improvements
reported in the groups receiving 1.0 mg/kg and 3.0 mg/kg.
The most common adverse event in patients receiving baminercept was
headache. Transient mild-to-moderate flu-like symptoms were observed in 9
patients (25 percent) within 24 hours after the first dose of baminercept.
However, these symptoms responded well to acetaminophen and tended not to
recur with subsequent doses. No serious, drug-related adverse events were
reported in this study.
About Biogen Idec
Biogen Idec creates new standards of care in therapeutic areas with high
unmet medical needs. Founded in 1978, Biogen Idec is a global leader in the
discovery, development, manufacturing, and commercialization of innovative
therapies. Patients in more than 90 countries benefit from Biogen Idec's
significant products that address diseases such as lymphoma, multiple
sclerosis, and rheumatoid arthritis. For product labeling, press releases and
additional information about the company, please visit www.biogenidec.com.
Safe Harbor
This press release contains "forward-looking statements" regarding Biogen
Idec's development of baminercept that are based on current expectations and
assumptions that are subject to risks and uncertainties. Only a small number
of research and development programs result in commercialization of a product.
Factors which could cause actual results to differ materially from Biogen
Idec's current expectations include the risk that results observed in the
Phase IIa trial may not be predictive of the results to be obtained in the
additional studies that would be necessary to demonstrate baminercept to be
safe and effective in the treatment of patients with RA. In addition, the
company may not be able to meet applicable regulatory standards or regulatory
authorities may fail to approve baminercept; and the company may encounter
other unexpected hurdles. For further information regarding factors, risks and
uncertainties relating to Biogen Idec's drug research and development and
other activities, please refer to the filings Biogen Idec has made with the
Securities and Exchange Commission, including the "Risk Factors" section of
Biogen Idec's Quarterly and Annual Reports, copies of which may be obtained at
www.biogenidec.com. Biogen Idec assumes no obligation to update and
specifically disclaims any duty to update the information in this press
release for any reason, except as required by law, even as new information
becomes available or other events occur in the future. All forward-looking
statements in this press release are qualified in their entirety by this
cautionary statement.